Yet more evidence that the antivaccine trope of “too many too soon” is nonsense

One of the more persuasive talking points repeated ad nauseam by the antivaccine movement is the “too many too soon” trope. The idea behind this bit of propaganda is that, thanks to the expansion of the childhood vaccine schedule over the last 30 years, today’s children are getting too many vaccines too soon, and these vaccines “overwhelm” the infant’s immune system, leading to all the dire conditions and diseases for which antivaxers blame vaccines: autism (even in dogs!), asthma and autoimmune diseases, premature ovarian failure, diabetes, sudden infant death syndrome (SIDS), the deaths of young people, and even abusive head trauma (previously known as shaken baby syndrome). Part and parcel of this idea is that unvaccinated children are healthier than vaccinated children, no matter how low into the muck of pseudoscience antivaxers have to go to dredge up “evidence” to support this idea.

The idea of “too many too soon” makes “intuitive” sense in that to the layperson it would seem that throwing too many challenges to the immune system in too short a time in a developing baby might be harmful, but we have copious evidence that this is not so. For one thing, even though there are more vaccines, the design and manufacture of vaccines are much more precise, such that the number of antigens children receive today by age 4 is at least 25-fold fewer than it was 30-40 years ago even as children receive vaccines against many more diseases. When you compare the number of antigens in the vaccine schedule (a few hundred at most) to the many thousands of antigens they encounter just by living, the ridiculousness of the “too many too soon” talking point becomes obvious. It’s not just that, though. Scientists have actually done studies. For instance, in 2013 a study was published showing no association between total antigen exposure and the risk of autism or maximum antigen exposure at one visit (number of shots given in a single visit) and autism risk. It was about as resoundingly negative a study as I’ve ever seen. Basically, the current vaccine schedule is safe and effective and evidence-based.

So is the one that I’m going to talk about here, one that I discovered from Twitter and news reports:

Some parents may be afraid that babies and toddlers get too many vaccines all at once, but a new study can help put such worries to rest.

It found that kids who got more vaccines were not any more likely to get unrelated infections than kids who got fewer vaccines, or who had them spaced out more than recommended.

There was not much reason to think that vaccinating children might make them somehow more susceptible to diseases in general, but the researchers said it is important to keep testing, to reassure parents.

OK, before I start discussing the study itself, let me just express my irritation at this framing of the reason to keep testing, to reassure parents. While this might be somewhat true for fence sitters, those who’ve heard the lies of antivaxers and become concerned because they don’t know whether the fear mongering has any basis in science and evidence, but even to reach them probably doesn’t make continuing to do these studies over and over again justifiable, either scientifically or ethically, once the evidence has become overwhelming that vaccines to not “overwhelm” babies’ immune systems. The reason is simple. The parents responsible for the myth of “too many too soon” will not be reassured by a study. They will not be reassured by five negative studies. They will not be reassured by 50 negative studies. They will not be reassured by 5,000 negative studies. Hell, they probably won’t be reassured by 5 million negative studies. Worse, they’ll continue to spread antivaccine misinformation that will continue to influence a subset of parents to start to doubt vaccines.

The children making up the cases and controls were taken from a cohort drawn from the Vaccine Safety Datalink (VSD). Antivaxers often claim that the Vaccine Adverse Event Reporting System (VAERS) is a passive system and, as such, can miss many adverse events and lament the absence of an active reporting system. By “passive” reporting system, I mean one that doesn’t actively look for cases and relies on parents and health care providers reporting adverse events. In contrast, “active” systems look for cases actively by looking for them, either through a database or other means. VSD is an active surveillance system. Yes, contrary to a frequent antivaxer claim that there are no active surveillance systems for vaccine safety looking for adverse events. There are, in fact, three: one run by the FDA called PRISM (Post-licensure Rapid Immunization Safety Monitoring System) and the VSD (Vaccine Safety Datalink), which is run by the CDC, and the Clinical Immunization Safety Assessment (CISA) Project, which studies of vaccines safety with an emphasis on those who might be at risk of adverse events—something antivaccine activists say isn’t done.

So here’s how cases were identified:

VSD data sets were first used to identify children born between January 1, 2003, and September 31, 2013. For inclusion, children had to be continuously enrolled in the health plan from age 6 weeks through 23 months. Children were excluded if they did not have at least 2 well-child visits before their first birthday, had a medical contraindication to vaccination, or if they had received vaccines not universally recommended by the Advisory Committee on Immunization Practices.10 Eligible children were followed up through age 47 months or until disenrollment from their health care organization; the final day of follow-up was December 31, 2015.

Then to identify cases of non-vaccine-preventable infections:

From ages 24 through 47 months, potential non–vaccine-targeted infections were identified in VSD data sets using International Classification of Diseases, Ninth and Tenth Revisions, Clinical Modification (ICD-9/10-CM) codes in the ED and inpatient settings (eTable 1 in the Supplement). The list of outcome ICD codes was based on a Danish cohort study by Sørup et al,11 which tested a similar hypothesis. Non–vaccine-targeted infection outcomes included lower respiratory infections, upper respiratory infections, gastrointestinal infections, and other viral and bacterial infections. In the cohort, the first occurrence of an ICD code for a non–vaccine-targeted infection from ages 24 through 47 months was identified as a potential incident case.

You don’t have to go into all the epidemiology-speak, but you do have to know what a case control study is, because that’s what this is. In a case control study, cases (patients with a disease or condition under study) are matched as closely as possible in pertinent risk factors (e.g., age, sex, race, other risk fctors) to controls who do not have the disease or condition. Then, the two groups are compared for differences in a specific risk factor for which they were not matched. You don’t need to know the details, but you should know that each case was matched to up to four controls, and that ultimately there were 193 cases with non–vaccine-targeted infections and 751 controls without non–vaccine-targeted infections studied. Antigen exposure was measured as the number of immunogenic proteins and polysaccharides in each vaccine (eTable 3 in the Supplement).

So what did they find. Figure 2 shows the odds ratio for non-vaccine-targeted diseases

Notice the plot on the right. Notice how all the error bars cross 1.0. That means there was no statistically significant difference between cases and controls in the chance of getting a disease not targeted by vaccines. In other words, cumulative exposure to antigens did not correlate with these diseases. Neither did another factor commonly invoked by antivaxers:

That’s right. The estimated maximum single-day antigen exposure doesn’t correlate with the risk of disease not targeted by vaccines either. The authors did a number of secondary analyses and confirmatory analyses to make sure that they didn’t miss anything, and they didn’t.

When the VSD system was created in 1990, its charge was 2-fold: to study vaccine safety and to strengthen the public’s confidence in vaccines. The study by Glanz et al9 is an example of fulfilling the first charge. However, the VSD has not been as successful at strengthening the public’s confidence in vaccines. The rates of vaccine refusal and delay have increased, and clinicians encounter vaccine-hesitant parents with increasing frequency.3,4

The present study provides further reassurance to parents that the US childhood vaccination schedule is safe in terms of not being associated with an increased risk of non–vaccine-targeted infections, yet the small but vocal minority of antivaccine groups may not be satisfied by the evidence provided through VSD and other vaccine safety surveillance. For example, insistence by such groups that vaccines cause autism persists, despite overwhelming science to the contrary. Although the VSD and other mechanisms, such as the Post-Licensure Immunization Safety Monitoring system, must continue to study the scientific questions, closer attention must also be paid to fulfilling the VSD’s second purpose of strengthening the public’s confidence in vaccines.

This passage bothers me. The purpose of the VSD is primarily scientific, to identify adverse reactions to vaccines through active surveillance. O’Leary and Maldonado are naive in the extreme if they think any number of scientific studies are going to reassure antivaxers. We already have more than enough studies to know that vaccines don’t cause autism or any of the other conditions antivaxers blame them for. We know that vaccines are safe and effective. That is not to say that we shouldn’t continue to study them through the VSD, looking for adverse reactions, but reinventing the wheel by doing in essence the same study over and over and over again and getting negative results over and over and over again are not the answer. Finding better ways to communicate those findings to the public is. In particular, we need to recognize that the hard core antivaxers will not be swayed by anything that comes out of the VSD or any other government-maintained database. That’s why it’s important to inoculate (if you’ll excuse the term) those who might be susceptible to the antivaccine message against the misinformation and pseudoscience that drive the antivaccine movement.

40 Comments

I don’t know why but this piece brought to mind Jonathan Swift. I am sure he would have had a recipe for overwhelming Irish babies immune system by slow roasting. All the loons that believe this tripe are being lead by flappers like the health stranger and the others of his ilk

I slightly disagree about the effect on parents. I agree antivaccine activists won’t be reached by data, but they’re a small minority. Many parents do want reassurance – basically, they are scared and want to know they’re doing the right thing – andthjs can help.

As you point out, the too many too soon myth does appeal to many parents. Aside from your points, watching five syringes prepared can be scary to parents on an emotional level.

Having studies like this can help. Does that justify it scientifically is a different question.

I agree with Dorit here. The people who are loud enough about their anti-vax feelings to attract Orac’s attention are fanatically devoted to that cause. It’s one of their three greatest weapons, along with fear, surprise, and ruthless efficiency. The main thing they hide with their loudness is that there aren’t very many of them.

Far more common are the parents who do a bit of looking online and find the scaremongering of the hard-core anti-vax crowd. Being able to show these parents a couple of relevant studies allows most of them to see the scaremongering for what it is.

I’m in a Facebook group called Vaccines on the Fence and it’s heartening to see how many people who are scared by the misinformation of the anti-vaxxers can be reassured once they’re shown the real science, or a couple of relevant studies, as Eric says there. Unfortunately, it’s also quite depressing how many parents are led astray by anti-vaxxers in various parenting groups on Facebook. My feeling is that parents (particularly mothers) who struggle with anxiety issues are rich fodder for anti-vaxxers.

I’m glad to hear that. I focus on vaxxers so I hear little from fence sitters.

Anxiety in new parents is probably one of the factors that makes them so vulnerable to anti-vax propaganda. I also think that personality issues play a part- when you hear so many who believe that they know more than experts despite their own lack of education, it seems powerful. Indeed, some alt med proselytisers discuss the cult of the expert which asserts that experts know little, that they’re merely pawns of the powers-that-be: any parent wiling to scour the internet with a heart full of love can do much better.

Sites like AoA are rife with researchers who deconstruct SB research in ways congruent to their own wishes. Similarly, journalists disentangle the twisted web of Pharma ‘crime’ ( see Autism Investigated)
Some of them write books published by ((shudder))

A famed woo-meister says, ” Do your homework”
I say, ” If only!”

Certain people are more prone to believing conspiracies and not trusting authorities in science. But that’s a whole ‘nother dissertation.

Wouldn’t provoking the immune system result in fewer secondary infections? What would an “overwhelmed” immune system be? I keep coming back to HIV–the virus displaces T cell DNA and prevents normal replication. But that has nothing to do with vaccines.

Without getting into the deep immunology topics, there is a point at which the immune system stops caring because it’s under heavy assault. We (meaning me at the blood bank) see that happen when we transfuse people massive quantities of blood that is not exactly their type. (For example, an O-negative man is given O-positive blood.) There’s a point at which the person will not produce antibodies against the “offending” blood type. Someone with more knowledge on immunology than me would be better able to explain this.

I don’t doubt that vaccinating babies is safer, as they would not develop specific immune responses with autoimmune side effects. What I doubt is that there is an adequate way to make a study of the effectiveness at various ages, because I am not sure that protection is studied in babies.

Well, DeStefano was a co-author of this paper and the CDC was involved, so that means everyone probably sat around a table in a conference room shredding all the contrary data, throwing it into a giant garbage can and setting it on fire.

The non-sheeple know better about vaccines inducing immune system overwhelmingness.

I was going to say all the hardcore “ain’t nuttin’ ever gonna git me to vaccinate” crowd are almost certainly crying about this being CDC data–making the study worthless. But I like your shredding imagery better for the ‘spiracy folk out there who will never believe anything that supports vaccination.

My daughter got her 6-month shots the other day. Pentacel (diphtheria, haemophilus influenzae type B, pertussis, polio, and tetanus), Hepatitis B (last dose of series), Prevnar13 (against 13 serotypes of pneumococcus), rotavirus (last in a series), and her first influenza (next one in a month). She is a happy and healthy baby. She’s almost crawling now. She hasn’t missed any milestones. Even if she does, we are going to love her unconditionally and not use her as a pawn in a game of scaring people away from what science and evidence has shown to save lives.

I posted a picture of her little legs about to get poked, along with the syringes ready to be used. Some antivaxxer showed up and berated me for giving her so many, citing that there have been no “long term” studies of the effects of that many vaccines being given at the same time. They then blocked me when I berated them for using scare tactics to scare people away from vaccines and for a clarification of what “long term” is.

That’s the game they play. They’ll say it’s “too many too soon” but won’t say how much is “just enough and just in time.” In fact, ask some of the most hardened antivaxxers who say that they are not “anti-vaccine” but instead claim to be “pro safe vaccine” have a very hard time telling you which vaccines are safe.

I know that the era of expertise died when the internet fully arrived, but there is still something to be said for expert knowledge. Don’t confuse knowledge with opinion.

No need for games just best practice.Check out Japan…this country has strict laws about what age infants get exposed to so many Vaccinations. The result from this hold back until nearly age three is a miniscule amount of children (and parents) that are forced for the rest of their lives into Autism. Don’t attack me just check this Nation’s statistics against those of the USA. I have an associate in NY who was ignored by her children’s doctor/s after Autism set in to her child. She is an avid researcher and her doctor (who is a next door neighbor) will no longer talk to her or look her in the eye. Why? She has brought the child back from Autism to within 5% of normal…How? She used chelation therapy over several years. Nothing wrong with vaxxes but plenty wrong if administered in series before age 3 or so. After that go for it fil the little suckas with anything you like and sit and hope.

“Check out Japan…this country has strict laws about what age infants get exposed to so many Vaccinations.”

Ah, a variation of the most idiotic anti-vaccine lie every perpetuated. Dear silly person that is not what happened. Here is the actual factual PubMed indexed study with the story:
Expert Rev Vaccines. 2005 Apr;4(2):173-84.
Acellular pertussis vaccines in Japan: past, present and future.

Which says: “An antivaccine movement developed in Japan as a consequence of increasing numbers of adverse reactions to whole-cell pertussis vaccines in the mid-1970s. After two infants died within 24 h of the vaccination from 1974 to 1975, the Japanese government temporarily suspended vaccinations. Subsequently, the public and the government witnessed the re-emergence of whooping cough, with 41 deaths in 1979. This series of unfortunate events revealed to the public that the vaccine had, in fact, been beneficial.”

In short, you cannot blame a vaccine for a death if the vaccine was not actually given. Especially if the babies actually died from the disease. Also, you can use teh Googles to learn that Japan’s infant schedule is pretty much like every other developed country. Yes, they actually vaccinate for pertussis, tetanus and diphtheria starting at three months of age.

Which says: “In Japan, measles vaccine coverage has remained low, and either small or moderate outbreaks have occurred repeatedly in communities. According to an infectious disease surveillance (2000), total measles cases were estimated to be from 180,000 to 210,000, and total deaths were estimated to be 88 [11,12]. Measles cases are most frequently observed among non-immunized children, particularly between 12 to 24 months.”

Quick math quiz, Ian: is 24 months before after the third birthday?

Lesson: Japan is not a good example of good public health policy decisions. Kids actually die!

“She has brought the child back from Autism to within 5% of normal…How? She used chelation therapy over several years.”

Wow, you are gullible. Here is an idea, look up what happened to Abubakar Tariq Nadama when he got chelation therapy for autism. I understand Andy Cutler, with a PhD in chemical engineering, was a big proponent of chelation for both autism and heart disease. Can you tell what happened to Dr. Cutler? Just use teh Googles.

“She has brought the child back from Autism to within 5% of normal…How? She used chelation therapy over several years.”
As Joe in “The A Word” likes to say, let me see. Antivaxxers don’t all agree on what component or timing of vaccines leads to autism. Your citing of chelation “therapy” (You are really forcing me into using lots of quotation marks.) indicates that you blame the minuscule amounts of mercury and aluminum for causing autism. Thimerosal, an organic compound in which the mercury is bound, is cleared rapidly buy the kidneys, and besides, it is rarely encountered anymore. The trivial amount still found in a few formulations has never triggered my (proven) thimerosal allergy, so it must be really small to have escaped notice by my immune system. Aluminum is as I recall the third most common element here above Earth’s crust. It’s everywhere, and no doubt is in our food in nontrivial amounts. It must also be taken in by the tendency of small children to put things in their mouths. To assume that the amount that must surely be taken into blood and tissue is far less than the amount used in vaccines is ludicrous. So using a dangerous drug to remove mercury that isn’t there and aluminum that is normally present in everybody will reverse structural changes in the brain. i believe it may possibly work, and while you are proving it, I will just wait for NASA to bring me back some of that delicious cheese that the moon is made of.
Others here have addressed the inane “5%” figure, but I will put in my 2 % of a dollar here . There is no numerical scale for autism vs.normal. I am assuming that by “normal” you mean “neurotypical”. In any case, if you meet one autistic person, you have met one autistic person. There is no one size fits all description.
I have an autism spectrum condition and have spent my life living among your so-called normals. I am not impressed.

I am and always have been a very rational person. I caused problems as early as age 6 in Sunday School and was an atheist by age 8 or so. Still, when my eldest child had to be re-immunized in first grade when the school lost her shot record, I was extremely upset and was sure she would be harmed in some way. This was in 1975, and there was no internet and no antivax movement–none I’d heard of anyway. The doctor was amused by my fears, which only made me more suspicious–and angry as it seemed condescending to me at the time when he chuckled at my questions.

I relate this because I find it interesting (and puzzling) that I had a reaction over 40 years ago that is so similar to what we are seeing now. There must be something psychological going on here. I distincly remember that no amount of reassurance given at the time gave me any comfort. I continued to vaccinate my subsequent children without hesitation, but always harbored worries about my daughter. Only many years later, after becoming an active skeptic, did I fully let go of the fear from that experience. In my case, the internet helped this process, but I think how easily it can go the other way. I have a science background for one thing, in addition to an innate curiosity and skepticism.

There are certain reactions which are built into our pre-language brain and which we share with all mammals. The thing is that these thoughts occur in an entirely different part of the brain than the one that you used to write this excellent comment.

We have a natural distaste for anything that breaks our skin, and we have a natural distaste for anything that’s obviously sick, dead, or rotten. I suspect that’s what you were feeling–the idea that someone wanted to put something disgusting into your child’s body.

Well, no, I didn’t think the immunizations were “disgusting”, or “sick, dead, or rotten”. It was just the fear that comes from not understanding enough science at the time and thinking she would be overdosed or some such. I was fine with the initial immunizations. Polio was still a threat when I was born and I had a smallpox vaccination as a young child, so I was very happy to vaccinate. What does surprise me is that I wouldn’t listen to or believe the doctor, who was actually a very nice man. Wherever this fear comes from, it is powerful and overrides reason easily. This is the point which my story only illustrates.

I think the whole thing may have been avoided if the doctor has bothered to explain instead of chuckling at my ignorance.

See also this : https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3824286/
Fig. 1 is the japanese vaccination schedule. Looks like infants get exposed to quite a few vaccinations before age 3.
This myth is likely a deformation from temporary suspensions of specific vaccines like the pertussis one.

I discovered an anti-vaxxer live streaming a “critique” of this study, the conclusion of which was that it is junk science simply because the control group was not an un-vaccinated placebo. Yes he expected that in a case control study. He admits he was completely confused by it all yet he still felt he understood it well enough to discuss it on air. An interesting, albeit painful, insight into the anti-vaccine mindset and poor understanding of the subject matter. The link if you want to listen: https://www.youtube.com/watch?v=vbXYomV-tWI#t=26m55s

Its not the antigens in vaccines causing the health damage (autism, brain injuries, immune disorders etc). Its the ADJUVANTS. This is because, in general, vaccine injury is mediated by inflammation, and inflammation is what adjuvants do. Adjuvants are specifically designed to cause inflammation, which can persist (for months or years). And the aluminum adjuvants, being particulate, can travel to vulnerable tissues/organs like the brain. These tissues cannot tolerate chronic inflammation during early stages of development. Inflamation during development causes life-long health problems and increases disease risk later in life.

The idea that vaccine injury should be correlated to number of antigens is not based on any accepted theory, model or evidence. Its a poor hypothesis to test, but falsifying it does not imply that vaccines and all their other ingredients are safe. Its a poor hypothesis because, as the pro-vaccine argue, children are naturally exposed to antigens all the time. There is no good reason to believe that the antigens are the problem.
The Glanz 2018 paper you cite has two big problems:
1) the analysis was performed on the basis of antigen exposure, which is not relevant.
2) selection bias (healthy user bias specifically). Parents observing vaccine injury in their child at age 0, 2, 4, 6, or 12 months tend to stop or reduce vaccination. These injured children are consequently allocated to a low-vaccine exposure (low antigen exposure) cohort. This makes all the results unreliable.

I misspoke by referring to “cohort” since this was a case-control study. Please forgive me! But I maintain that selection bias will affect the results of this case control study, to bias the results toward finding no association.

Healthy user bias is a severe problem with observational studies of vaccine safety. Vaccine critics that understand the impossibility of avoiding healthy user bias will indeed never be convinced by these observational studies. That is the scientifically correct position!

In his textbook Vaccines, Offit et al state: ““Confounding by contraindication is especially problematic for non-experimental designs. Specifically, individuals who do not receive vaccine (e.g., because of a chronic or transient medical contraindication or low socioeconomic group) may have a different risk for an adverse event than vaccinated individuals (e.g., background rates of seizures or sudden infant death syndrome may be higher in the unvaccinated). Therefore, direct comparisons of vaccinated and unvaccinated children is often inherently confounded and teasing this issue out requires understanding of the complex interactions of multiple, poorly quantified factors.”
–Vaccines, 5th ed, 2008, page 1631

“Its not the antigens in vaccines causing the health damage (autism, brain injuries, immune disorders etc). Its the ADJUVANTS.”

Then tell your friends it cannot be the MMR vaccine!

Also, you forgot one big step: in order to prove what in vaccines causes something… you need to prove the vaccines cause that thing. There is no evidence that autism is correlated with autism:
Vaccine. 2014 Jun 17;32(29):3623-9. doi: 10.1016/j.vaccine.2014.04.085.
Vaccines are not associated with autism: an evidence-based meta-analysis of case-control and cohort studies.

In the future when you mention the “increase” in autism, please be clear about which version of DSM was being used to diagnose autism. Remember, you need to make sure it is the same criteria at all times. You need to make sure there are no outstanding confounders in your data, and different diagnosis criteria is a huge confounder.

You just cited the Taylor 2014 paper, which is a review/metaanalysis of MMR and thimerosal studies. It is completely irrelevant to concerns about aluminum adjuvant toxicity or aluminum-containing vaccines. Neither MMR nor thimerosal contain aluminum. Even the title of this paper is misleading by referring to “vaccines” in the plural. Really, it concerns only ONE vaccine: the MMR, and ONE vaccine ingredient: thimerosal.

A link between MMR and autism is debatable, because of healthy user bias (a type of selection bias). All the MMR-autism studies are observational, and therefore may be affected by this bias. I am aware that dozens of studies have been published on MMR-autism, and they consistently observe no association. It seems like a powerful case. However, healthy user bias is a systematic bias that will likely affect them all. Also, MMR studies are particularly susceptible because MMR is given after most other vaccines. That tends to increase the potential for the bias.

Its not the antigens in vaccines causing the health damage (autism, brain injuries, immune disorders etc). Its the ADJUVANTS.

To add to Chris’s smackdown of you, thank you for confirming you’re antivaccine. You goalpost shifted from antigens to adjuvants. This is typical. Once one thing is refuted as a cause, you simply move on to the next item without checking if vaccines DO cause those problems.

I personally never moved any goalposts, because I have always been critical of the “antigen hypothesis”. Antigens are everywhere and children are exposed to god-knows-how-many every day. But thats irrelevant anyway, because Changing a working hypothesis in view of new evidence is a fundamental part of the scientific method. That is very different from moving goalposts. Please learn the difference.

Chris didnt smack anything down, because he cited an irrelevant paper (Taylor 2014). This paper only looks at MMR and thimerosal, neither of which contain aluminum. Taylor 2014 cannot be cited in a discussion about aluminum adjuvant.